Cancer treatment for people with PALB2 mutations
People with an inherited PALB2 mutation who have been diagnosed with cancer may have different treatment options than people without a mutation. To learn more about standard of care treatment options for specific types of cancer, visit our section on Cancer Treatment by Cancer Type.
If you have an inherited PALB2 mutation, have been diagnosed with cancer and any of the situations below apply to you, you may want to speak to your doctor about your medical options. You may also consider enrolling in a clinical trial studying which treatments work best for people with an inherited PALB2 mutation.
- You have metastatic prostate cancer
- You have advanced ovarian cancer
- You have advanced pancreatic cancer
- You have been diagnosed with breast cancer
- You are making breast cancer surgical decisions
PARP inhibitors are a type of targeted therapy that work by blocking a protein used to repair damaged DNA. They were initially developed to treat cancers in people with an inherited BRCA1 or BRCA2 mutation. Since then, research and additional FDA approvals have expanded use of PARP inhibitors to more situations. People with a PALB2 mutation who have been diagnosed with cancer may want to ask their doctor about PARP inhibitor therapy.
The PARP inhibitor, Lynparza (olaparib) has received FDA-approval to treat men with metastatic, castration-resistent prostate cancer, who have a mutation in PALB2 or another gene linked to a certain type of DNA damage repair. Lynparza may be used to treat men whose prostate cancer has progressed on enzalutamide (Xtandi) or abiraterone (Zytiga).
Several PARP inhibitors have been approved to treat ovarian cancers at different stages of the disease. In some situations, a tumor biomarker test known as an HRD test ("hemologous recombination deficiency") can help women with an inherited PALB2 mutation and advanced ovarian cancer learn if they may benefit from a PARP inhibitor.
- Advanced cancer which has recurred after third-line treatment:
- HRD testing can help women with an inherited PALB2 mutation and advanced ovarian cancer which has recurred after three lines of treatment learn if they may benefit from the PARP inhibitor Zejula (niraparib).
- Maintenance therapy after first-line treatment
- HRD testing can help women with an inherited PALB2 mutation and advanced ovarian cancer learn if they may benefit from the PARP inhibitor Lynparza?(olaparib) in combination with bevacizumab as maintenance therapy after first-line platinum chemotherapy.
- Zejula is approved for maintenance therapy in women with advanced ovarian, fallopian tube, or primary peritoneal cancer who had a complete or partial response to first-line platinum-based chemotherapy. Zejula for maintenance therapy does not require an HRD test.
- Maintenance therapy after treatment of recurrent cancer
- Zejula and Rubraca (rucaparib) are both approved for maintenance therapy in women with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum based chemotherapy.
Although PARP inhibitors have not specifically received FDA approval to treat panceratic cancer in people with PALB2 mutations, the American Society of Medical Genetics released a paper suggesting that people with PALB2 mutations and cancer should be considered for the same treatments and clinical trials as people with a BRCA1 or BRCA2 mutation. The PARP inhibitor Lynparza is FDA approved for maintenance treatment of pancreatic cancer in people with a BRCA mutation whose disease has not progressed after completing first-line platinum-based chemotherapy.
Although PARP inhibitors have not specifically received FDA approval to treat breast cancer in people with PALB2 mutations, the American Society of Medical Genetics released a paper suggesting that people with PALB2 mutations and cancer should be considered for the same treatments and clinical trials as people with a BRCA1 or BRCA2 mutation. Below are guidelines for PARP inhibitors for treating breast cancer in people with a BRCA1 or BRCA2 mutation.
- Treatment for metastatic breast cancer: The PARP inhibitors, Lynparza (also known as olaparib) and Talzenna (also known as talazoparib) both have received FDA approval for treating metastatic breast cancer caused by a BRCA mutation.
- Treatment for early-stage breast cancer: Based on results from a large clinical trial, experts recommend one year of the PARP inhibitor olaparib for people with early-stage, HER2-negative breast cancer who have an inherited BRCA mutation and who are at high risk for recurrence.
Because of the high risk for a second breast cancer diagnosis, women who are diagnosed with breast cancer who test positive for an inherited mutation in PALB2 may choose bilateral mastectomy rather than lumpectomy and radiation. Mutation carriers who undergo mastectomy are less likely to develop a second breast cancer.
If you are a person with a PALB2 mutation, you can find peer support through the following resources:
- FORCE blog: Read stories submitted by people with PALB2 mutations
- Video: FORCE members with a PALB2 mutation
- FORCE's Peer Navigation Program will match you with a volunteer who shares your mutation and situation and provide you with a free resource guide.
- Register for the FORCE Message Boards to connect with others who share your situation. Once you register, you can post on the Share Your Mutation board to connect with other people who carry a PALB2 mutation and the Diagnosed With Cancer board to connect with other people who have been diagnosed.
- Contact the FORCE impact leaders in your area to link to local support groups and other resources.
- Attend a virtual support meeting in your area.
The following cancer treatment studies are open to people with an PALB2 mutation.
Advanced solid tumors of any type
- NCT04171700: A Study to Evaluate Rucaparib in Patients With Solid Tumors and With Deleterious Mutations in HRR Genes (LODESTAR). This study is evaluating the response of rucaparib in patients with various solid tumors and with deleterious mutations in Homologous Recombination Repair (HRR) genes.
- NCT02264678: Ascending Doses of Ceralasertib in Combination With Chemotherapy and/or Novel Anti Cancer Agents. This is a study of ceralasertib administered orally in combination with chemotherapy regimens and/or novel anti-cancer agents, to patients with advanced cancer.
- NCT02286687: Talazoparib in Treating Patients With Recurrent, Refractory, Advanced, or Metastatic Cancers and Alterations in the BRCA Genes. This phase II trial studies how well talazoparib works in treating patients with cancers that have returned after a period of improvement, do not respond to treatment, or have spread to other parts of the body, and have alterations in the breast cancer, early onset (BRCA) genes.
- NCT03344965: A Phase 2 Study of Olaparib Monotherapy in Metastatic Breast Cancer Patients with Germline or Somatic Mutations in DNA Repair Genes (Olaparib Expanded). Olaparib (Lynparza) is a type of treatment known as a PARP inhibitor, which is approved for metastatic breast cancer in people with a BRCA mutation. This study is looking at how well olaparib works in people with a PALB2 or other mutation.
- Breast Cancer Treatment in Women with PALB2 Mutations. The PALB2 Study is an international research study to better understand breast cancer treatment among women with a PALB2 gene mutation. Participants are asked to complete online or paper study questionnaires (every two years for 10 years) and share their family history, medical, and genetics records.
- NCT02401347: Talazoparib Beyond BRCA (TBB) Trial. People with an ATM mutation who have metastatic triple-negative breast cancer may qualify for this study. Talazoparib (Talzenna) is a type of treatment known as a PARP inhibitor, which is approved for metastatic breast cancer in people with a BRCA mutation. This study is looking at how well talazoparib works in people with a PALB2 or other mutation.
- NCT02975934: A Study of Rucaparib Verses Physician's Choice of Therapy in Patients With Metastatic Castration-resistant Prostate Cancer and Homologous Recombination Gene Deficiency (TRITON3). TRITON3 study is looking at how well the PARP inhibitor rucaparib (Rubraca) works for men with a BRCA or PALB2 mutation and advanced prostate cancer.
- NCT03442556: Docetaxel, Carboplatin, and Rucaparib Camsylate in Treating Patients With Metastatic Castration Resistant Prostate Cancer With Homologous Recombination DNA Repair Deficiency. This trial studies how well docetaxel with carboplatin followed by rucaparib camsylate works in treating patients with metastatic castration resistant prostate cancer. The study is open to men with a PALB2 or other inherited mutation.
- NCT03012321: Abiraterone/Prednisone, Olaparib, or Abiraterone/Prednisone + Olaparib in Patients With Metastatic Castration-Resistant Prostate Cancer With DNA Repair Defects. This is a phase II study in men with metastatic castration resistant prostate cancer (mCRPC) open to men with a PALB2 or other mutation.
- NCT04858334: Olaparib or Placebo in Patients with Surgically Removed Pancreatic Cancer who have a BRCA1, BRCA2 or PALB2 Mutation (APOLLO). The purpose of APOLLO is to compare the usual approach (observation) to treatment for one year with a drug called olaparib, in patients with a BRCA1, BRCA2 or PALB2 mutation and resectable pancreatic cancer.
- NCT03404960: Niraparib + Ipilimumab or Nivolumab in Progression Free Pancreatic Adenocarcinoma After Platinum-Based Chemotherapy (Parpvax). This study will look at the effectiveness, safety, and anti-tumor activity (preventing growth of the tumor) of the drugs Niraparib with either Ipilimumab or Nivolumab on patients and their pancreatic cancer.
- NCT04493060: Niraparib and Dostarlimab for the Treatment of Germline or Somatic BRCA1/2 and PALB2 Mutated Metastatic Pancreatic Cancer. This study looks at how well the PARP inhibitor niraparib and the immunotherapy drug dostarlimab work together in treating patients with metastatic pancreatic cancer, who also have an inherited or tumor mutation in one of the following genes: BRCA1, BRCA2, PALB2, BARD1, RAD51c, RAD51d.
Visit our Research Search and Enroll Tool to find additional cancer treatment studies.